The present invention is generally directed to an efficient method to remove acyl-groups appended by an ester linkage to the 2′-hydroxyl group present in paclitaxel-related molecules.
Paclitaxel (PAC) is an important anticancer drug. However, because of its low water solubility, the formulations needed to deliver PAC by intravenous injection are less than ideal. Thus, considerable attention has been directed toward improving the aqueous solubility of PAC, particularly by pursuing prodrug strategies that take advantage of the C7 or C2′ hydroxyl groups for such incorporations. Protecting groups that have been used most frequently during these manipulations include silyl,1,2 monochloroacetyl3 (CAC), and trichloroacetyl.4 Because of its greater reactivity, several investigators have also been able to modify the C2′ hydroxyl group directly, i.e. without protecting the C7 hydroxyl functionality.5-10 
Selective manipulation of the hydroxyl groups present in paclitaxel (PAC) and in 10-deacetylpaclitaxel (DAP) to produce stable analogs and water-soluble prodrugs, has received considerable attention over the course of the last twenty years of PAC-related research.1-11 Deutsch et al.3 have shown that among all of the hydroxyl groups present in this family of compounds, the C2′ OH is the most reactive toward acylation. When PAC is treated with carbonyldiimidazole, the resulting C2′ acylated intermediate can additionally form an oxazolone derivative, an interesting side-reaction more recently encountered by de Groot et al.4 as well. Amino acid derivatives connected via ester linkages at the C2′ position are considerably less stable than when connected at C7 such that the C2′ arrangement has been extensively pursued during prodrug strategies. Likewise, Mathew et al.5 has exploited the instability of C2′ esters to produce C7-amino acid esters of PAC by partial, selective hydrolysis of the 2′,7-bis-substituted PAC analogs at pH 7.4. Harada et al.6 have speculated that the instability of the C2′ amino acid esters is due to steric repulsion of the bulky groups attached to C2′ and C3′ as well as to an electronic effect from these types of esters' amino groups. The latter has also been previously implicated by zhao et al.7 and more recently by Pendri et al.8 who suggested more specifically that protonation of the amino group could serve to assist attack of the C2′ acyl functionality by external nucleophiles due to a simple inductive effect. Other investigators have further postulated that C2′ esters of PAC are particularly susceptible to cleavage by various hydrolytic enzymes present in vivo.